A Multiple Ascending Dose Study of MEDI7247 in Advanced or Metastatic Solid Tumors

December 27, 2019 updated by: MedImmune LLC

A Phase 1/1b Multicenter, Open-label, Dose-escalation, and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumor Activity of MEDI7247 in Patients With Advanced or Metastatic Disease in Selected Solid Tumors

To assess safety and tolerability, describe the dose-limiting toxicities, assess the preliminary antitumor activity, determine the maximum tolerated dose (MTD) or the highest protocol-defined dose (maximum administered dose) in the absence of establishing the MTD, and a recommended dose for further evaluation of MEDI7247 in patients with selected advanced or metastatic solid tumor malignancies that have received at least 1 prior line of treatment.

Study Overview

Study Type

Interventional

Enrollment (Actual)

8

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Research Site
    • North Carolina
      • Huntersville, North Carolina, United States, 28078
        • Research Site
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 101 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Confirmed diagnosis of advanced or metastatic select solid tumors and either progression on or documented intolerance to standard therapies
  2. Age ≥ 18 years at the time of screening.
  3. Written informed consent and any locally required authorization
  4. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  5. At least 1 measurable target lesion by CT or MRI per RECIST Version 1.1 (excluding mCRPC)
  6. Adequate Liver Function: Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5 × ULN (upper limit normal), Albumin > 3 g/dL, and serum total bilirubin (TBL) ≤ 1.5 × ULN; (unless bilirubin rise is due to Gilbert's syndrome, hepatic metastases or of non-hepatic origin, in which case TBL ≤ 3 × ULN is allowed)
  7. Creatinine Clearance (CrCL) ≥ 40 mL/min
  8. Adequate Hematopoesis: Absolute Neutrophil Count (ANC) ≥ 1,500/μL, Platelets ≥ 100,000/μL, and Hgb ≥ 9 g/dL unassisted by transfusion or growth factor within 14 days of screening
  9. Provision of archival or fresh tumor tissue at screening
  10. Female patients of childbearing potential who are sexually active with a nonsterilized male partner must use at least one highly effective method of contraception, and must agree to continue using such precautions for 90 days after the last dose of investigational product.
  11. Nonsterilized male patients who are sexually active with a female partner of childbearing potential must use a male condom plus spermicide from 7 days post-screening and for 90 days after receipt of the last dose of investigational product.

Exclusion Criteria:

  1. Active central nervous system (CNS) metastases, unless adequately treated and patients have neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) and prednisolone 10 mg or less for more than 2 weeks prior to enrollment. For SCLC, a brain MRI scan that was conducted ≤ 28 days from Day 1 is required.
  2. Residual toxicity from prior anticancer therapy not resolved to NCI CTCAE v4.03 Grade 1, with the exception of alopecia/vitiligo at the time of first dose of investigational product. For patients previously receiving immunotherapy, toxicities that are unlikely to recover to Grade 1.
  3. Royal Marsden Hospital (RMH) prognostic score 2 and 3 at baseline.
  4. Treatment with anticancer therapy including chemotherapy, radiation therapy, immunotherapy, biologic, or any investigational therapy within 21 days, or prior palliative radiotherapy within 2 weeks of the first dose of investigational product.

5 Prior treatment with other Pyrrolobenzodiazepine-Antibody Drug Conjugates.

6 History of previous malignancies (except for locally curable cancers) unless a complete remission was achieved at least 3 years prior to study entry AND no additional therapy is required during the study period (except adjuvant hormonal therapy and bisphosphonate).

7. Failure to recover from major surgery or significant traumatic injury within 21 days of first dose of study treatment.

8 History of hepatic sinusoidal obstruction syndrome, also called veno-occlusive disease 9. History of capillary leak syndrome. 10 Blood transfusion within 14 days of study entry except when needed for disease related anemia.

11. New York Heart Association classes III-IV congestive heart failure or serious cardiac arrhythmia requiring treatment, history of myocardial infarction, unstable angina, vascular stent, or coronary artery bypass graft within 6 months of the first dose of investigational product. 12. Active human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infections at the time of screening.

13. Current severe active systemic disease including active concurrent malignancy 14. Pregnancy and/or breastfeeding at time of screening 15. Concurrent enrollment in anther clinical study involving an investigational treatment that is not an extension of another MedImmune study with the same investigational product.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: NSCLC-Sq/HNSCC
Patients with advanced or metastatic NSCLC-Sq or HNSCC who have recurrence after, or are refractory or intolerant to standard therapy, including at least one prior standard of care regimen (platinum-based for HNSCC). PDL-1 positive patients should have received previous PD-1 or PD-L1 inhibitor where available.
Subjects with advanced solid tumors will enroll into the respective arms to receive Medi7247 IV at prescribed dose and schedule
Experimental: Small Cell Lung Cancer
Patients with advanced SCLC who have recurrence after, or are refractory or intolerant to standard therapy, including at least one prior standard of care regimen.
Subjects with advanced solid tumors will enroll into the respective arms to receive Medi7247 IV at prescribed dose and schedule
Experimental: Colorectal Cancer
Patients with metastatic adenocarcinoma of the colon or rectum who have received and have progressed, or have documented intolerance, on prior thymidylate synthase inhibitor (eg, 5-fluorouracil (5-FU), capecitabine, raltitrexed, tegafur-uracil (UFT), irinotecan, and oxaliplatin for metastatic disease. If patients progress within 6 months of their last dose of adjuvant therapy this should be considered as a line of therapy in the metastatic setting. Patients with known RAS wildtype tumors must have received and progressed, or have documented intolerance, on anti-EGFR antibody. Patients with microsatellite instability-high or deficient mismatch repair tumors, must have received and progressed, or have documented intolerance on a PD-1 inhibitor, or PD-1 inhibitor plus cytotoxic T-lymphocyte antigen-4 inhibitor treatment where available.
Subjects with advanced solid tumors will enroll into the respective arms to receive Medi7247 IV at prescribed dose and schedule
Experimental: Pancreatic Ductal Adenocarcinoma
Patients with unresectable, locally advanced or metastatic PDAC who have recurrence after, or are refractory or intolerant to standard therapy, including at least one prior line of treatment.
Subjects with advanced solid tumors will enroll into the respective arms to receive Medi7247 IV at prescribed dose and schedule
Experimental: Metastatic Castration-Resistant Prostate Cancer
Patients with mCRPC who have received prior treatment with abiraterone or enzalutamide, with or without a prior taxane-based chemotherapy in the mCRPC setting.
Subjects with advanced solid tumors will enroll into the respective arms to receive Medi7247 IV at prescribed dose and schedule
Experimental: Other advanced/metastatic target expressing solid tumors
Patients with advanced or metastatic solid tumors not defined by other treatment arms who have positive expression of the protein target and have exhausted all approved therapies
Subjects with advanced solid tumors will enroll into the respective arms to receive Medi7247 IV at prescribed dose and schedule

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Occurrence of Adverse Events
Time Frame: From time of informed consent through 90 days post end of treatment
To assess the occurrence of adverse events
From time of informed consent through 90 days post end of treatment
Occurrence of Serious Adverse Events
Time Frame: From time of informed consent through 90 days post end of treatment
To assess the occurrence of serious adverse events
From time of informed consent through 90 days post end of treatment
Occurrence of Dose Limiting Toxicities
Time Frame: During the evaluation period of 21 days post first dose
To assess the occurrence of toxicities and abnormal laboratory results that may limit further dose administration
During the evaluation period of 21 days post first dose
Number of patients with changes in laboratory parameters from baseline
Time Frame: From time of informed consent through 90 days post end of treatment
To assess serum chemistry, hematology, urinalysis and coagulation parameters
From time of informed consent through 90 days post end of treatment
Number of patients with changes in vital signs parameters from baseline
Time Frame: from time of informed consent through 21 days post last dose
to assess changes in vital signs
from time of informed consent through 21 days post last dose
Number of patients with changes in electrocardiogram results from baseline
Time Frame: from time of informed consent through 21 days post last dose
to assess changes in ECG
from time of informed consent through 21 days post last dose
Percentage of patients with changes in laboratory parameters from baseline
Time Frame: from time of informed consent through 90 days post end of treatment
to assess changes in serum chemistry, hematology, urinalysis, and coagulation parameters
from time of informed consent through 90 days post end of treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
MEDI7247 maximum observed concentration (Cmax)
Time Frame: From first dose through 90 days post end of treatment
To characterize MEDI7247 single agent Pharmacokinetics
From first dose through 90 days post end of treatment
MEDI7247 terminal half life (t1/2)
Time Frame: From first dose through 90 days post end of treatment
To characterize single agent MEDI7247 pharmacokinetics
From first dose through 90 days post end of treatment
MEDI7247 area under the concentration/time curve (AUC)
Time Frame: from first dose through 90 days post end of treatment
To characterize single agent MEDI7247 pharmacokinetics
from first dose through 90 days post end of treatment
MEDI7247 clearance
Time Frame: from first dose through 90 days post end of treatment
to characterize the single agent MEDI7247 pharmacokinetics
from first dose through 90 days post end of treatment
Number of subjects who develop anti-drug antibodies
Time Frame: first dose through 90 days post end of treatment
To characterize MEDI7247 immunogenicity
first dose through 90 days post end of treatment
Best Overall Response
Time Frame: From time of informed consent and up to 90 days post end of treatment
To assess antitumor activity of MEDI7247
From time of informed consent and up to 90 days post end of treatment
Objective Response Rate (ORR)
Time Frame: From time of informed consent and up to 2 years after last subject in
To assess antitumor activity of MEDI7247
From time of informed consent and up to 2 years after last subject in
Time to Response (TTR)
Time Frame: From time of informed consent and up to 90 days post end of treatment
To assess antitumor activity of MEDI7247
From time of informed consent and up to 90 days post end of treatment
Duration of Response (DoR)
Time Frame: From time of informed consent and up to 2 years after last subject in
To assess antitumor activity of MEDI7247
From time of informed consent and up to 2 years after last subject in
Progression Free Survival (PFS)
Time Frame: From time of informed consent and up to 2 years after last subject in
To assess the antitumor activity of MEDI7247
From time of informed consent and up to 2 years after last subject in
Disease Control (DC)
Time Frame: From time of informed consent and up to 2 years after last subject in
To assess antitumor activity of MEDI7247
From time of informed consent and up to 2 years after last subject in
Overall Survival (OS)
Time Frame: From time of informed consent and up to 2 years after last subject in
To assess antitumor activity of MEDI7247
From time of informed consent and up to 2 years after last subject in

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 20, 2018

Primary Completion (Actual)

December 10, 2019

Study Completion (Actual)

December 10, 2019

Study Registration Dates

First Submitted

December 21, 2018

First Submitted That Met QC Criteria

January 17, 2019

First Posted (Actual)

January 22, 2019

Study Record Updates

Last Update Posted (Actual)

December 30, 2019

Last Update Submitted That Met QC Criteria

December 27, 2019

Last Verified

December 1, 2019

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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